With the constantly deepening recognition on the pathogenesis of diseases in the cell level, gene therapy has become the study focus of scientists. For gene therapy, exogenous gene DNA or RNA fragments are introduced into target cells or tissues to correct or make up for the defects of genes, close or inhibit the expressions of abnormal genes, and thereby fulfilling the aim of treating diseases. Gene therapy, as a new treatment means, can treat multiple diseases, including cancers, hereditary diseases, infectious diseases, cardiovascular diseases and autoimmune diseases, in which the gene therapy for cancers is the main application field. The vectors for gene delivery mainly comprise viral vectors and non-viral vectors. The viral vectors, such as recombinant adenovirus vectors, are very effective in transfection efficiency and can target most of cells, and thereby getting certain superiority in the gene delivery. However, it will cause in-vivo immunoreaction and contains transcriptional virus gene, which may cause genetic recombination or complement in vivo to further harm human bodies. Compared with the viral vectors, the non-viral vectors are limited in transfection efficiency, but have the advantages of no infectiousness, no limits to vector capacity, controllability in chemical structure, easy preparation in large quantities and so on, hence, more and more people have been increasingly appreciating the non-viral vectors.
Cationic liposomes have the cell-like structure and the characteristic of a biological membrane and they can be degraded in vivo, cationic liposomes can protect the biological activity of the fragment of their carried genes, which have become non-viral gene transfection vectors with the clinical potential. Under the structure of the liposome, genes can be compressed to form complexes, and the complexes are delivered to lesion tissues or cells. Since 1987, after Felgner, et al. carried out transfection successfully on cells, such as COS-7 by utilizing N-[1-(2,3-dioleoacyloxy)propyl]-N,N,N-trimethyl ammonium chloride (DOTMA) for the first time, the liposome has developed to the most popular gene transfer means except for the retrovirus vectors, and particularly, is mainly applied in the treatment of tumors, cystic fibrosis and other diseases. Because there are some limitations for the liposome, such as high cytotoxicity and non-obvious targeting on organs and undefined gene delivery mechanism, the liposome cannot be widely applied. Hence, people have devoted themselves to various constructions and chemical modifications of the cationic liposome, trying to seek a gene therapeutic drug with high efficiency and low toxicity.
The liposome has developed for nearly 30 years, which has formed the perfect liposome vector systems from widely used quaternary ammonium salt head and guanidine group head to polyamine head cationic lipid, however, there are many problems for these vector systems, for example, the transfection efficiency of mediated genes needing be improved; no directional recognition on target tissues; after the cationic liposome/DNA complex entering into cells, nucleic acid being constrained in endosome and difficult to release, which is adverse to its expression in cytoplasm or cell nucleus, so it cannot achieve the purpose of treatment. The Chinese patent application CN103613516A, 2014 Mar. 5 discloses a preparation method for Gemini cationic lipids and use thereof in drugs or gene delivery, the vector has certain cytotoxicity due to its poor biodegradability with the double head structure, resulting in restrictions to the aspect of in-vivo gene transfection.